The proposed project deals with the ultrastructural, functional and synthetic properties of vascular endothelium and smooth muscle under normal conditions and in response to physiological and pathological stimuli. Using endothelial cultures, we will examine synthesis, function, and metabolism or vasoactive compounds including prostaglandin and angiotensin; the response of endothelial cells to possible toxic stimuli such as endotoxin, cholesterol, and anoxia; factors influencing endothelial growth and migration; and surface properties of endothelial cell membranes. In vivo studies will include mechanisms and kinetics of endothelial proliferation in response to injury. These studies will be relevant to understanding the pathogenesis of inflammation, thrombosis, atherosclerosis, and tumor growth. Studies on glomerular permeability will examine the distribution of anionic charges within the glomerular capillary wall and the effect of molecular charge on the permeability of molecules in normal animals and in animals with experimental glomerulonephritis and nephrotic syndrome. Methods used are tissue culture, electron microscopy, ultrastructural cytochemistry, autoradiography, immunoflourescence microscopy, and in vitro perfusion methods in well defined experimental models. BIBLIOGRAPHIC REFERENCES: Sholley, M.M., Gimbrone, M.A. and Cotran, R.S.: Effects of irradiation on migration and mitosis of endothelial cells in culture. Fed. Proc. 35(3):680, 1976 (Abstract). Sholley, M.M., Gimbrone, Jr., M.A., and Cotran, R.S.: The relationship of leukocytic infiltration to neovascularization of the cornea. Anat. Rec., 184:528-529, 1976.